Reproductive Risk Factors and Coronary Heart Disease in the Women’s Health Initiative Observational Study

Abstract

Background Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk, however their contribution to CHD risk stratification is uncertain. Methods and Results In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥ 1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C-statistic, net reclassification index (or NRI with risk categories of <5%, 5–<10%, and ≥10% 10-year risk of CHD) and integrated discriminatory index (IDI) were assessed. Among 72,982 women [n=4607 CHD events, median follow-up=12.0 (IQR=8.3–13.7) years, mean (SD) age 63.2 (7.2) years], an age-adjusted reproductive risk factor model had a C-statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C-statistic increased from 0.726 to 0.730; IDI=0.0013, p-value < 0.0001). Net reclassification for women with events was not improved (NRI events=0.007, p-value=0.18); and for women without events was marginally improved (NRI non-events=0.002, p-value=0.04) Conclusions Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination and do not materially improve net reclassification.

Female infertility, infertility-associated diagnoses, and comorbidities: a review

“…The health implications of PCOS have been thoroughly documented, including an increased risk for endometrial cancer, metabolic disorders, cardiovascular disease, obesity, and a predisposition to insulin resistance or outright diabetes [16,[21][22][23][24][25][26]. Since PCOS makes women 10 times more likely to develop infertility, it is crucial to understand the connections between a diagnosis of PCOS and overall health [23].…”

“…The eight studies detailed in Table 5 show correlations between infertility and increased cardiovascular risk, higher myocardial infarction rates, higher insulin resistance, increased waist circumference, higher rates of central adiposity, increased diagnosis of metabolic syndrome, and increased risk of non-alcoholic fatty liver disease [16,[21][22][23][24][25][26]. These studies also show increased hospitalizations for various disease processes in women with a known history of PCOS [6].…”

The role of nurse practitioners in primary care in optimizing risk stratification for coronary heart disease in Canadian women: an integrative review

“…Reproductive factors provide an early window into a woman's CHD risk; however, their contribution to CHD risk stratification is uncertain (Parikh, 2016). The impact of reproductive complications during pregnancy on developing subsequent CHD remains unclear and will be reviewed below.…”

“…A landmark WHI-OS explored the association between reproductive factors and CHD (Parikh, 2016). The sample included 72 982 women with a mean age of 63 years and a total of 4607 CHD events (Parikh, 2016).…”

“…A landmark WHI-OS explored the association between reproductive factors and CHD (Parikh, 2016). The sample included 72 982 women with a mean age of 63 years and a total of 4607 CHD events (Parikh, 2016). A Cox proportional hazard model for CHD was developed and included age, pregnancy status, number of live births, age of menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥1 year, infertility cause, and breastfeeding (Parikh, 2016).…”